Drug resistance aiding spread of dysentery-causing bacteria

Antibiotic resistance has helped a type of bacteria which causes dysentery to spread into countries undergoing rapid development and industrialization worldwide, a study of the bacteria's DNA suggests.

The study by an international group of researchers, including scientists from the Oxford University Clinical Research Unit in Vietnam, found that the bacterium Shigella sonnei first became established in Europe a few centuries ago, but in the last few decades has spread to the rest of the world.

A key factor in the spread was a rise in multidrug resistance – the ability of the bacteria to survive exposure to a wide array of antibiotics, they report in the journal Nature Genetics.

Because S. sonnei is easily transmitted and has high levels of drug resistance, the researchers argue that antibiotic treatment and better sanitation alone will not be sufficient for controlling the disease. Vaccine development will be crucial.

Dysentery is a disease primarily associated with developing countries. More than one million people, mostly young children, are estimated to die from dysentery caused by Shigella each year.

The bacterium Shigella flexneri has been the most common form of Shigella to cause dysentery in developing countries, with S. sonnei more prevalent in industrialized countries. Yet this pattern is beginning to change, with S. sonnei becoming increasingly common as developing countries rapidly industrialize.

The team looked at the S. sonnei's genetic evolution to investigate why the bacterium was spreading so effectively. They found that only a few types of genes were selectively evolving over time, particularly those involved with drug resistance. This suggests that a major driver in the spread of the bacterium is its apparent ability to become resistant to drug treatment.

'Since S. sonnei originated, we found there have been three, independent, yet closely related lineages that have spread,' says senior author Dr Stephen Baker from the Oxford University Clinical Research Unit in Vietnam. 'The two most recent lineages have been continually evolving to become increasingly resistant to antimicrobials. 

'Our data is consistent with antibiotic resistance as being a main driver of the spread and persistence of S. sonnei around the world, stressing that antibiotics are not a long-term solution for the elimination of this global health problem.'

First author Dr Kathryn Holt of the University of Melbourne says: 'Although S. sonnei is a relatively new species of bacterium, during its spread it has diversified into an array of different distinguishable clones or strains found right across the world. This is hard to see using traditional methods, but by sequencing the genomes of over 100 different forms of the bacteria, we were able to get a glimpse into its past and really start to understand how it is evolving and moving around the world.

'We compared the S. sonnei family tree and geographical locations of the different strains to determine when and where this bacterium first emerged and why it has become such a problem in industrialized countries with increasing access to clean water. Traditionally we associate dysentery with contaminated water and lack of industrialization.'

As developing countries become more industrialized the numbers of infections with dysentery-causing Shigella flexneri are known to decline, associated with improved health, lifestyle and perhaps most importantly access to clean water. But the incidence of Shigella sonnei actually increases.

'Our research emphasises the importance of a vaccine against Shigella,' says lead author Professor Nicholas Thomson from the Wellcome Trust Sanger Institute, near Cambridge. 'The combination of increased incidence and antibiotic resistance of S. sonnei means that a vaccine will be increasingly important for the long-term control and prevention of dysentery.'

The work was supported by the Wellcome Trust and the Victorian Government in Australia.